Bicarbonate is a major constituent of water and wastewater. The acid-base balance in the human body is regulated by pulmonary and renal mechanisms. Bicarbonate is the main ion connecting these two regulative mechanisms.
A conventional method for the determination of bicarbonate ion is of measuring the partial pressure of carbon dioxide in a liquid and hydrogen ion concentration. The concentration of bicarbonate ion can be determined by calculating from the above values. However, the method is disadvantageous in the simultaneous measurement of the partial pressure of carbon dioxide and pH of the liquid.
Another conventional method is of utilizing the conversion of bicarbonate ion into carbon dioxide in acidic conditions, and measuring the volume of the evolved carbon dioxide. In general, a large scale equipment is necessary for measuring the volume of gas accurately, and accordingly, this method is disadvantageous to the measurement of a large number of samples.
There are three clinically approved methods to measure bicarbonate ion in blood, serum and plasma samples. The first approach is the calculation of bicarbonate concentration from measured pH and pCO2 levels. Mainly this is done using the Henderson-Hasselbalch equation. The second method is calculation of the base excess/deficit from pCO2 and pH. The idea of base excess/deficit is based on the premise that the degree of deviation from the normal buffer availability can be calculated independently of CO2 changes. The third method is determination of the calculated pH difference from measured pH and pCO2.
Compounds of the type capable of forming complexes with analyte molecules like urea, thiourea, guanidine, substituted guanidines, arginine, amidine compounds, creatinine are known from WO 01/55719 A, WO 02/14465 A, U.S. Pat. No. 5,283,333 A and U.S. Pat. No. 5,030,728 A. The compounds are characterized by the structural element

Structural elements of the type —C═N—C═N— are able to bind two hydrogen atoms of an analyte molecule via hydrogen-bridge bonds (compare structure Vla in U.S. Pat. No. 5,030,728). The analyte molecules possess at least two hydrogen atoms in close vicinity, able to bind to the above structural element.
In contrast, bicarbonate possesses a single hydrogen atom and three oxygen atoms.

In sum, the oxygen atoms possess seven lone electron pairs, of which five are located in the molecular plane and are able to bind hydrogen of “hydrogen bond donors” in a planar host compound via hydrogen bridge-bonds. Further, bicarbonate possesses one hydrogen atom, able to bind to one “hydrogen bond acceptor”. Thus, it is obvious that, due to its steric positions of hydrogen bond donors and acceptors, the structural elements (i.e., —C═N—C═N—) known in the art are not suitable to selectively bind bicarbonate.
Moreover, the host compounds of the prior art possess electron-rich cavities that bind only neutral and cationic guest molecules, whereas, in order to bind anions such as bicarbonate, the host compound must feature a sufficient number and correct orientation of hydrogen bond donor groups.
Bicarbonate is known to have low solubility in non-aqueous solutions or solvents. For some applications, however, it is necessary or advantageous to introduce bicarbonate in non-aqueous solutions. For example, bicarbonate can be utilized as a catalyst or a buffer in organic solvents. Further applications involve the use of bicarbonate as a base or simply as a reagent in chemical reactions.
Over the past 30 years, chemists have used phase transfer agents to solubilize polar reactants such as hydroxide in order to conduct useful reactions in organic solvents (W. E. Keller, Compendium of Phase-Transfer Reactions and Related Synthetic Methods, Fluka AG (Buchs, Switzerland, 1979); E. V. Dehmlow, S. S. Dehmlow, Phase Transfer Catalysis, Verlag Chemie (Weinheim, Germany, 1983)). Conventional phase transfer agents such as crown ethers and quaternary ammonium salts either bind the cation, e.g. sodium, to solubilize the anion as an ion pair, or they replace the hydrophilic cation with a lipophilic one. Because they do not selectively bind the anion, they cannot select a single anion for transport from water into the organic layer, if more than one anion is present.
Carbonate has been used as a base in many phase-transfer reactions (see the references above), but carbonate is so strongly hydrated that there is doubt that it is actually transported into the aqueous layer. Such reactions may actually occur at the solid-liquid or liquid-liquid interface. It has also been proposed that bicarbonate actually mediates these reactions, because it is less polar than carbonate and is present in equilibrium in the aqueous solution (E. Lissel, E. V. Dehmlow, Chem. Ber. 114, 1210 (1981)). A phase transfer agent that is specific for bicarbonate would resolve this problem.
Therefore, there is a need for compounds that selectively form complexes with bicarbonate, enabling the measurement of bicarbonate levels in body fluids and other liquids. There is also a need for phase-transfer agents which are capable of delivering bicarbonate to non-aqueous solutions.
Accordingly, it is an object of the present invention to provide compounds which are suitable as receptor compounds that reversibly bind bicarbonate.
Another object of the invention is to provide compounds which allow to determine bicarbonate levels in liquid samples, preferably by means of photometric methods.
A further object of the invention is to provide compounds which are suitable for the manufacture of optical sensors.
It is a further object of the invention to provide an optical sensor for the determination of bicarbonate in a liquid sample.
A further object of the invention is to provide compounds which are useful as phase-transfer agents for the delivery of bicarbonate to non-aqueous solutions.